“The Sequence Listing submitted in text format (.txt) filed on Nov. 14, 2013, named “13fpo-10-12US_sequencinglist.txt”, created on Nov. 11, 2013, 3.50 KB), is incorporated herein by reference.”
1. Field of the Invention
The present invention relates to a pharmaceutical composition for the prevention or treatment of atopy comprising the extract of Daphne genkwa, the fraction thereof, or the compound isolated from the same as an active ingredient.
2. Description of the Related Art
Atopy is a chronic relapsing dermatitis accompanying severe itch. Approximately 10˜15% of children have atopic dermatitis, and 90% of them get presumably better naturally within 5 years of breakout. This atopic dermatitis is generally improved when patients become adults, and is not coming back at least outwardly in approximately 30˜40% of them. However, the rest of them are still suffering dermatitis with such symptoms as dry skin, skin irritation and housewife's eczema whenever stimulated by irritants even as adults. Sensitive skin is characterized by low water retention, weak recovery power, hyperkeratinization, and itch, which therefore progresses easily to atopic skin.
The exact pathophysiology of atopy has not been completely understood, yet, and is only presumed to be attributed to genetic factors along with immunological and non-immunological mechanisms altogether. Most of atopy cases are extrinsic atopy, which is developed by IgE-related immune mechanism. There are many reports saying that delayed-type immune response caused by T-cell malfunction is responsible for this extrinsic atopy rather than specific allergen mediated immediate-type immune response. It has been recently reported that Th2 related cytokines including IL-4 which induce IgE generation from B cells are the causes of atopy (J S Kang et al., Inhibition of atopic dermatitis by topical application of silymarin in NC/Nga mice. intl immunopharm. (2008) 8. 1475-1480).
To treat atopy, ceramides, linoleic acids, vegetable oils or mineral oils, steroids including hydrocortisone, the materials which have been reinforced with anti-bacterial/anti-inflammatory activity, DNA synthesis inhibitors, cell hyper-proliferation inhibitors, and inflammation/itch suppressors have been proposed. However, the said materials can cause side-effects. For example, steroids can cause epidermal growth suppression, urea peroxides can cause over-irritation on skin, and antibiotics including anti-histamine agent can cause bacterial resistance and photosensitivity. Moreover, long-term administration of such drugs might bring more serious side effects such as telangiectasia and/or thickness of keratin. Gamma-linoleic acid, frequently used for relieving atopy these days (Korean Patent Publication No. 2000-0046633), is easily oxidized, indicating a problem of stability, and causes skin irritation strongly, so that it is not suitable for sensitive skin.
Therefore, natural substances have been focused recently to treat atopy, which are exemplified by Artemisia vulgaris extract (Korean Patent No. 10-0377262), the extract of Ganoderma lucidum, Ulmus pumila, Licorice, Poria, Sesamurn indicum L. and Opuntia ficus indica (Korean Patent No. 10-0517465), the extract of Evening primrose, Aloe, pyroligneous liquor, Violet, Jujube, pine mushroom, Aralia elata, Panax ginseng, green tea, Eucommia ulmoides, Rubus coreanus, Schisandra chinensis, Artemisia vulgaris, Taraxacum mongolicum, Saururus chinensis, Astragalus membranaceus, Prunella vulgaris, Pinus thunbergii, Scutellaria baicalensis and Achyranthes japonica (Korean Patent No. 10-0451444), the extract of blue Perilla frutescens and red Perilla frutescens (Korean Patent No. 10-0454752), the extract of Castanea crenata, Coicis semen, Schisandra chinensis, Platycodon grandiflorum, Raphanus sativus, Liriope platyphylla and Acorus gramineus (Korean Patent No. 10-0483539), the extract of lavender, Eucalyptus globulus and tea tree oil (Korean Patent No. 10-0597997), etc. Loranthus parasiticus, Albizzia julibrissin, Xanthium strumarium, and malt are also known to have an effect on atopy. However, these natural substances are weaker in treatment effect and even though they demonstrate some treatment effect they also cause allergic reaction especially on sensitive skin, which limits them in use.
Thus, it is highly requested to develop a safer and more effective substance than the conventional agents for the improvement and treatment of atopy.
In the course of study to screen a material that has an excellent effect in improving atopy from natural substances, the present inventors found out that the extract of Daphne genkwa, the fraction thereof, or genekwadapnin and yuanhuacine, the compounds isolated from the same, could increase the secretion of cytokine that converts Th1/Th2 imbalance resulted from atopic disease by acting on immune cells and epithelial cells, and further confirmed their effects on the improvement of atopy in the mouse model having atopic disease, leading to the completion of the present invention.